Tissue regeneration in humans is extremely limited and constitutes a major challenge to the repair of damaged organ function. A number of organs rely on undifferentiated stem and progenitor cells for tissue regeneration. However, it is unclear if resident stem cells are capable of regenerating the full mass of tissue required for a given injury. Furthermore, stem cells have not yet been identified for a number of tissues, and in those tissues in which stem cells have been identified, the factors required to induce their propagation and differentiation to acquire the fates of cells in these tissues are not fully understood. Thus, there is a need for methods of inducing well defined differentiated cells of known identity to contribute to cell replacement and tissue regeneration in vivo. Moreover, propagation of such cells ex vivo can be used as cell based therapies upon delivery in vivo. Such methods are also applicable to modeling human diseases ex vivo (eg. skeletal, neuronal, cardiac, pancreatic, hepatic diseases and the like) and elucidating the underlying defects. In addition drugs capable of ameliorating the human disease phenotype can be screened using such disease models.